Dual effects of neurokinin on calcium channel currents and signal pathways in neonatal rat nucleus tractus solitarius

Neurokinins, such as substance P (SP), modulate the reflex regulation of cardiovascular and respiratory function in the CNS, particularly in the nucleus tractus solitarius (NTS). There is considerable evidence of the action of SP in the NTS, but the precise effects have not yet been determined. Voltage-dependent Ca2+ channels (VDCCs) serve as crucial mediators of membrane excitability and Ca2+-dependent functions such as neurotransmitter release, enzyme activity and gene expression. The purpose of this study was to investigate the effects of neurokinins on VDCCs currents (ICa) in the NTS using patch-clamp recording methods. In 142 of 282 neurons, an application of [Sar9, Met(O2)11]-substance P (SSP, NK1 receptor agonist) caused facilitation of L-type IBa. Intracellular dialysis of the Gαq/11-protein antibody attenuated the SSP-induced facilitation of IBa. In addition, phospholipase C (PLC) inhibitor, protein kinase C (PKC) inhibitor and PKC activator attenuated the SSP-induced the facilitation of IBa. In contrast, in 115 of 282 neurons, an application of SSP caused inhibition of N- and P/Q-types IBa. Intracellular dialysis of the Gβγ-protein antibody attenuated the SSP-induced inhibition of IBa. These results indicate that NK1 receptor facilitates L-type VDCCs via Gαq/11-protein involving PKC in NTS. On the other hand, NK1 receptor inhibits N- and P/Q-types VDCCs via Gαq/11-protein βγ subunits in NTS.